CN106074464A - Cannabidiol application in preparation treatment gout medicine - Google Patents
Cannabidiol application in preparation treatment gout medicine Download PDFInfo
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- CN106074464A CN106074464A CN201610414958.4A CN201610414958A CN106074464A CN 106074464 A CN106074464 A CN 106074464A CN 201610414958 A CN201610414958 A CN 201610414958A CN 106074464 A CN106074464 A CN 106074464A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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Abstract
The invention discloses cannabidiol application in preparation treatment gout medicine.Inventor finds the gout effect that cannabidiol tool is the strongest first, hyperuricemia mice serum uric acid level can be significantly reduced, Normal Mouse Serum uric acid level is not made significant difference, can significantly drop the toes swelling that suppression is induced by Monosodium urate, activity is better than allopurinol, and toxic and side effects is little.Present invention also offers the pharmaceutical preparation of cannabidiol treatment gout and corresponding pharmaceutical dosage form thereof, with conventional preparation method, the medicine of the various different dosage forms used clinically can be formed in, easy to use.
Description
Technical field
The present invention relates to Fructus Cannabis extract cannabidiol new application in medical science, concretely relate to cannabidiol and exist
Application in preparation treatment gout medicine.
Background technology
Goat is the class disease that internal purine metabolic disturbance causes, purine through a series of metabolic alterations, end form
The product become is uric acid.What physiological function uric acid does not has in human body, under normal circumstances, the uric acid 2/3 of internal generation by
Kidney is discharged, and 1/3 is discharged by large intestine.Internal uric acid is to constantly generate and draining, and therefore it remains certain in blood
Concentration.In the synthesis and catabolic process of purine, there is the participation of multiple enzyme, owing to the birth defect metabolism of enzyme occurs disorderly
Disorderly, make the synthesis of uric acid increase or discharge and reduce, all can cause hyperuricemia.When serum Uric Acid Concentration is too high, uric acid i.e. with
The form of sodium salt is deposited in joint, soft tissue, cartilage and kidney, causes the foreign body inflammatory reaction of tissue to become to cause gout
The seed of trouble.As treatment the most thoroughly can cause arthroncus, deformity, stiff, periarticular ecchymosis, tuberosity, concurrent gouty renal calculus, bitterly
Wind renal failure, the life of the internal organs disease threat patients such as gouty coronary heart disease, hyperlipidemia, hypertension, urinary system calculus
The straight termination causing life of life.
Along with our people's growth in the living standard, life-time dilatation, the change (food rich in nucleoprotein of dietary structure
Increase), the increase of overweight people, and the attention degree reinforcement etc. to primary disease, gout is the most no longer the rare disease of compatriots, and it is ill
Rate relatively increased about 15～30 times before 15 years.Gout is apt to occur in middle-aging male, but middle and aged women and young man at present
Sickness rate risen.Age of onset is many more than 50 years old (63%)；In gerontal patient, women sickness rate is higher than man
Property, and sickness rate improves 29% after 60 years old by 60 years old front 7%.CDC up-to-date report display,
The sickness rate of China's gout surpasses the world average level, and whole nation patient with gout is more than seven million people, and whole world goat patient is up to
1.3 hundred million.
The current kind of antigout drug is few, and clinical treatment is mainly with colchicine, nonsteroidal antiinflammatory drug, hormone, promotion
Urate excretion medicine (such as probenecid, sulfinpyrazone and benzbromarone) and suppression uric acid synthetic drug (such as allopurinol) are main.Acute
Stadium mainly applies drink tazettine, nonsteroidal antiinflammatory drug, hormone, and the catabasis mainly applies promotion urate excretion medicine, suppression urine
Acid synthetic drug.These medicines are the most defective in treatment.Weak curative effect, side effect become greatly the bottleneck of its clinical practice, and not
Can life-time service.More common Chinese patent medicine preparations treat pain phoenix, but drug effect is relatively low.So being badly in need of at present grinding
System and exploitation selectivity are strong, have no side effect, efficiently and gout will not be made to produce the anti-gout novel medical of bounce-back after drug withdrawal.
Cannabidiol (CBD) is that a kind of nontoxic of extraction from Fructus Cannabis floral leaf can be used for medicine, cosmetics, health food
The aldehydes matter of high added value.At present, the developed country such as Israel, the U.S., Britain has done raw material with it and has developed multiple
Special effect medicine and cosmetics.CBD is the non-additive composition in Fructus Cannabis, and tetrahydrocannabinol (THC) can be hindered human nerve system
System impact, and there is the pharmacologically actives such as spasmolytic, resisting rheumatoid arthritis, anxiety, it is known that can serve as treating epilepsy, glycosuria
The active component of the medicine of the diseases such as disease, hypoxic ischemic encephalopathy of newborn.
Summary of the invention
It is an object of the invention to provide the new application of cannabidiol, i.e. new opplication in pharmacy.
It practice, the present invention relates to cannabidiol application in the medicine of preparation treatment or prevention gout.
The invention still further relates to cannabidiol application in preparation fall blood uric acid medicine.
The invention still further relates to cannabidiol application in preparation treatment or prevention antihyperuricemic disease drug.
In order to be more fully understood that the essence of the present invention, pharmacological evaluation and result with cannabidiol illustrate that it is in system below
New application in medicine field.
1, prepare cannabidiol, but cannabidiol used is not limited to following preparation method obtains.
Taking cannabis, leaf, fiber crops bran or three's mixture, after remove impurity, drying, pulverize, CO2 is super faces extraction, second after remove impurity
Alcohol re-dissolved, lysate is pentane eluting after chromatography, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain Fructus Cannabis
Diphenol.
2, cannabidiol powder is taken, standby after diluting with sodium chloride.
3, the cannabidiol impact on hyperuricemia mice uric acid is observed with conventional pharmacological testing.
(1) choose body weight 18～22g Kunming mouse 60, male and female half and half, be randomly divided into 6 groups, often group 10, the most normally
Matched group, model group, positive drug allopurinol tablet (40mg/kg) group, cannabidiol large, medium and small (60mg/kg, 30mg/kg,
15mg/kg) dosage group.Gastric infusion, 1 time/d, Normal group and model group gavage such as give at capacity distilled water, the continuous 12d.
Last is administered 1h pneumoretroperitoneum injection hypoxanthine 10mg/kg, and after 1h, eyeball takes blood, and 3000r/min is centrifuged 10min, takes supernatant
Survey serum uric acid.
Test result indicate that, compare with Normal group, model group mice serum uric acid content is significantly raised, has significance
Difference (P ＜ 0.05), prompting modeling success.After giving cannabidiol, compare with model group, cannabidiol large, medium and small dosage group
All can significantly reduce mice serum uric acid content, difference has significance (P ＜ 0.05～0.01)；Compare with other purine sheet group,
Cannabidiol large, medium and small dosage group fall mice serum uric acid content effect is all better than other purine sheet group, and difference has significance (P
＜ 0.05).Prompting, cannabidiol significantly reduces effect to the Mouse Blood uric acid caused by hypoxanthine, and effect is better than other purine
Sheet.The results are shown in Table 1.
The impact of the hyperuricemia mice uric acid that hypoxanthine is induced by table 1 cannabidiol
Note: compare with normal control sample,△P ＜ 0.05, compares with model group,*P ＜ 0.05,**P ＜ 0.01, with allopurinol
Sheet group, compares#P ＜ 0.05.
(2) cannabidiol impact on the acid of normal mouse retention
Choosing body weight 18～22g Kunming mouse 40, male and female half and half, be randomly divided into 4 groups, often group 10, the most right
According to group, cannabidiol each large, medium and small (60mg/kg, 30mg/kg, 15mg/kg) dosage group.Gastric infusion, 1 time/d, the most right
Give to wait capacity distilled water, continuous 12d according to group and model group gavage.Last is administered 1h eyeball and takes blood, and 3000r/min is centrifuged
10min, takes supernatant and surveys serum uric acid.
Test result indicate that, compare with Normal group, after giving cannabidiol, mice serum uric acid is contained by each dosage group
Measure equal zero difference (P ＞ 0.05).Prompting, normal Mouse Blood uric acid is not made significant difference by cannabidiol.The results are shown in Table 2.
The impact on the acid of normal mouse retention of table 2 cannabidiol
(3) cannabidiol causes the impact of rat paw edema to micro-crystal type Monosodium urate crystallization (MSU).
The preparation of MSU: put by 5g uric acid in 1000mL boiling water, adjusts pH to 7.4 with NaOH, is heated to 95 DEG C.Put room temperature bar
Part cools down and is gently mixed, and filters and i.e. obtains MSU, and MSU is placed in 200 DEG C of high temperature sterilizes, faces the used time and is made into physiological saline solution
The suspension of 100mg/mL is standby.
Choose body weight 180～220gWistar male rat 60, be randomly divided into 6 groups, often group 10, i.e. normal control
Group, model group, positive drug allopurinol tablet group (40mg/kg), cannabidiol each large, medium and small (60mg/kg, 30mg/kg, 15mg/
Kg) dosage group.Gastric infusion, 1 time/d, Normal group and model group gavage such as give at capacity distilled water, the continuous 15d.Last
After being administered 1h, cause inflammation in Rat Right metapedes plantar subcutaneous injection 0.15mLMSU (100mg/mL), after measuring the right side before and after causing inflammation
Foot sole of the foot Zhou Jing.Observe and measure after injection pedal swelling situation and week thereof after 1h, 2h, 3h, 5h, 7h Rat Right the most in the same time
Footpath, calculates its swelling.Swelling degree of the paw=(t time Zhou Jing-t0Time Zhou Jing)/t0Time Zhou Jing × 100%.
Result shows, compares with Normal group, and model group rats swelling degree of the paw is significantly raised, has significant difference (P
＜ 0.01), prompting modeling success.Cannabidiol compares with model group, and each group all can significantly inhibit rat paw edema, and difference has
Having significance (P ＜ 0.05, P ＜ 0.01), compare with other purine sheet group, cannabidiol group suppression rat paw edema is better than the most fast
Purine sheet group, difference has significance (P ＜ 0.05).Prompting, the degree of rat paw edema caused by MSU is had substantially by cannabidiol
Inhibitory action, effect is better than other purine sheet.The results are shown in Table 3.
The impact on rat paw edema rate of table 3 cannabidiol
Note: compare with normal control sample,△△P ＜ 0.05, compares with model group,*P ＜ 0.05,**P ＜ 0.01, with allopurinol
Sheet group, compares#P ＜ 0.05.
The invention provides with cannabidiol as active component, for treating the pharmaceutical preparation of gout.This pharmaceutical preparation is
With cannabidiol for effective active composition, and include other adjuvant components acceptable on pharmaceutics.Described pharmaceutical preparation
Including oral agents and injection, wherein oral agents includes capsule, oral liquid, tablet, drop pill, granule etc., and injection type includes
Injection dosage form and freeze-dried powder injection type etc..When preparing oral formulations, available auxiliary type agent can be starch, paste
The conventional filler such as essence or cyclodextrin, sucrose, stearate.Lyophilized injectable powder can pass through aseptic spray drying, cryogenic vacuum
Prepared by the methods such as dry, lyophilization.The later stage preparation technology of each preparation and equipment all belong to the routine techniques of pharmaceutical field, this
Bright this is not construed as limiting, therefore not describes in detail at this.
Could be aware that from result above, it is an advantage of the current invention that:
1, known compound cannabidiol has been excavated new medical application by the present invention, has opened up a new application neck
Territory.
2, prove that cannabidiol has the strongest gout effect by serial experiment, hyperuricemia can be significantly reduced little
Mus serum uric acid level, does not makes significant difference to Normal Mouse Serum uric acid level, can significantly drop the foot that suppression is induced by Monosodium urate
Toe swelling, activity and allopurinol are suitable, and toxic and side effects is little.Cannabidiol has the wind action of significantly treatment and prevention pain.
3, the cannabidiol safety non-toxic of the present invention, pharmacological action is strong, imply that good prospect in medicine.
4, the present invention products material abundance, inexpensive, have no toxic and side effects, preparation technology is simple, and can make mouth
Oral dosage form, injection type, tablet etc., easy to use, injection can make intramuscular injection and intravenous injection.
Detailed description of the invention
Below by embodiment, the present invention is described in further detail, but embodiment is not to the technology of the present invention side
The restriction of case.
Embodiment 1
Taking cannabis, leaf, after remove impurity, drying, pulverize, CO2 is super faces extraction, ethanol re-dissolved after remove impurity, lysate warp
Pentane eluting after chromatography, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain cannabidiol.
Take cannabidiol 100 grams (crossing 80 mesh sieves), add 60 grams of microcrystalline Cellulose, cross 80 mesh sieve three times, mix homogeneously, spray
Enter 95% ethanol solution, soft material processed, cross 40 mesh sieves and pelletize, 60 DEG C of dry half an hour, be sub-packed in 3# capsule, plastic-aluminum combined bag
Dress, makes capsule.
Embodiment 2
Taking cannabis, leaf, the mixture of fiber crops bran, after remove impurity, drying, pulverize, CO2 is super faces extraction, and after remove impurity, ethanol is again
Dissolving, lysate is pentane eluting after chromatography, collects eluent, concentrating under reduced pressure, vacuum drying, pulverizes, obtain cannabidiol.
Take cannabidiol powder, admixture doses 5～the dried starch of 20% and 1～the magnesium stearate of 5%, blended, system
Grain, is dried, tabletting, makes tablet.
Embodiment 3
Repeat embodiment 2, have following difference: take cannabidiol powder, add sucrose water and the preservative of convention amount, surely
Determine the adjuvants such as agent.Filtration, sterilizing, be distributed in 10mL bottle, make oral liquid.
Embodiment 4
Repeat embodiment 2, have following difference: take cannabidiol powder, add water for injection and dissolve, add 2.0 ‰ and live
Property charcoal, stirring, filter, continue with 0.45 μm, 0.22 μm microporous filter membrane classified filtering, supplement water for injection, be sub-packed in cillin bottle
In, lyophilization, recharge high-purity nitrogen, jump a queue, gland, packaging, make injection.
Claims (3)
1. cannabidiol application in the medicine of preparation treatment or prevention gout.
2. cannabidiol application in preparation fall blood uric acid medicine.
3. cannabidiol application in preparation treatment or prevention antihyperuricemic disease drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610414958.4A CN106074464A (en) | 2016-06-14 | 2016-06-14 | Cannabidiol application in preparation treatment gout medicine |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610414958.4A CN106074464A (en) | 2016-06-14 | 2016-06-14 | Cannabidiol application in preparation treatment gout medicine |
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| CN106074464A true CN106074464A (en) | 2016-11-09 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110064030A (en) * | 2019-05-30 | 2019-07-30 | 厦门梓素生物科技有限公司 | One kind extract for treating gouty arthritis medicinal application of CBD containing cannabidiol |
| CN110101804A (en) * | 2019-05-30 | 2019-08-09 | 厦门梓素生物科技有限公司 | A kind of epilepsy drugs combination of the extract containing cannabidiol and preparation method thereof |
| CN111683655A (en) * | 2017-12-29 | 2020-09-18 | Tgc网络公司 | Cannabidiol dosage forms |
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| WO2010126501A1 (en) * | 2009-04-29 | 2010-11-04 | University Of Kentucky Research Foundation | Cannabinoid-containing compositions and methods for their use |
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2016
- 2016-06-14 CN CN201610414958.4A patent/CN106074464A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010126501A1 (en) * | 2009-04-29 | 2010-11-04 | University Of Kentucky Research Foundation | Cannabinoid-containing compositions and methods for their use |
Non-Patent Citations (1)
| Title |
|---|
| 魏平等: "《临床速查掌中宝丛书-内分泌科临床速查掌中宝》", 31 January 2015, 军事医学科学出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111683655A (en) * | 2017-12-29 | 2020-09-18 | Tgc网络公司 | Cannabidiol dosage forms |
| CN110064030A (en) * | 2019-05-30 | 2019-07-30 | 厦门梓素生物科技有限公司 | One kind extract for treating gouty arthritis medicinal application of CBD containing cannabidiol |
| CN110101804A (en) * | 2019-05-30 | 2019-08-09 | 厦门梓素生物科技有限公司 | A kind of epilepsy drugs combination of the extract containing cannabidiol and preparation method thereof |
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| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Xu Chenfeng Inventor after: Hu Chengyue Inventor before: Chen Tianrui Inventor before: Hu Chengyue |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20161109 |
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| RJ01 | Rejection of invention patent application after publication |